CERTAIN 5H-ISOXAZOLO{8 5,4-d{9 PYRIMIDIN-4-ONES

ABSTRACT

Outstanding herbicidal activity is exhibited by the respective members of the group of new isoxazolopyrimidines that are included within the general formula: WHEREIN R and R&#39;&#39;, which may be the same or different, are each members of the group consisting of lower (one to four carbon atoms)-aliphatic, lower (three to six carbon atoms)cycloaliphatic and trifluoromethyl radicals; AND THE METALLIC AND AMINE SALTS THEREOF.

United States Patent Gibbons 51 July 25,1972

I CERTAIN 5H-ISOXAZOLO[5,4-

D lPYRlMlDlN- i-ONES Loren K. Gibbons, Medina, N.Y.

|73| Assignce: F MC Corporation, New York, N.Y.

[22] Filed: April 23, I970 [21] Appl. No.: 31,414

I72] Inventor:

Rajagopalan et al., Tetrahedron, 23(8), 3,541- 3,543 (1967). Taylor et al., J. Org. Chem 29(8), 2,116- 2,l20 (1964).

Primary Examiner-Alex Mazel Assistant Examiner-R. J Gallagher Attorney-Pauline Newman, Eugene G. Seems, Henry R. Ertelt and Ralph M. Watson [57] ABSTRACT Outstanding herbicidal activity is exhibited by the respective members of the group of new isoxazolopyrimidines that are included within the general formula:

0 N) R, wherein R and R, which may be the same or different, are each members of the group consisting of lower (one to four carbon atoms)aliphatic, lower (three to six, carbon atoms)- --cycloaliphatic and trifluoromethyl radicals;

and the metallic and amine salts thereof.

13 Claims, No Drawings 1 CERTAIN SH-ISOXAZOLO[ 5,4-D1PYRIMIDIN-4-ONES SUMMARY OF THE INVENTION v The isoxazolopyrimidines embraced within the formula:

R NH

wherein R and R have the significance given above (and the metallic and amine salts thereof), are characterized, as a class,

by the outstanding herbicidal activity which they respectively exhibit. When applied at agriculturally accepted rates, either to soil previous to plant emergence or to the foliage of living' plants or to the soil in which said plants are growing, they effect excellent herbicidal control. However, they, differ somewhat among themselves in the degree of herbicidal activity that they respectively exhibit, and in the selectivity of the plants against which they act. Consequently, the particular members of that class that I now prefer to employ in the 'practice of my invention are:

3,6-Diisopropyl-5H-isoxazolo[5,4-d]pyrimidin-4-one 6-Ethyl-3-isopropyl-5 H-isoxazolo[5,4-d]pyrimidin-4-one 6-tert-Butyl-3-isopropyl-5 l-I-isoxazolo[5,4-dlpyrimidin-4- one 3-tert-Butyl-6-isopropyl-5l-l-isoxazolo[ 5 ,4-d1pyrimidin-4- one 3-tert-Butyl-6-ethyl-5 H-isoxazolol5,4-d1pyrimidin-4-one 6-tert-Butyl-3-propyl-5l-l-isoxazolo[5,4-d1pyrimidin-4-one 3,6-Diethyl-5H-isoxazolol5,4-d1pyrimidin-Lone 3-tert-Butyl-6-methyl-5H-isoxazolo[5,4-d1pyrimidin-4-one 3 upon the identity of the plant or plants to be controlled in each that l have found to be highly effective are:

6-tert-Butyl-3-methyl-5H-isoxazolo[5,4-d]pyrimidin-4-one 3-Ethyl-6-isopropyl-5 l-l-isoxazolo[ 5,4-d]pyrimidin-4-one 6-lsopropyl-3-propyL5 H-isoxazolo[ 5,4-d1pyrimidin-4-one 3-Ethyl-6-methyl-5H-isoxazolol5,4-d1pyrimidin-4-one 3-Ethyl-6-tert-butyl-5 H-isoxazolo[5,4-d1pyrimidin-4-one 6-Ethyl-3 methyl-5l-l-isoxazolo[5,4-djpyrimidin-4-one 6-Methyl-3-propyl-5l-l-isoxazolol5,4-dlpyrimidin-4one 3-Butyl-6-ethyl-5l-l-isoxazolo[5,4-d1pyrimidin-4-one 6-CycIopropyl-3-propyl-5H-isoxazolo[5,4-d]pyrimidin-4- one 3-tert-Butyl-6-propyl-5H-isoxazolo[5,4-d1pyrimidin-4-one 6-Butyl-3-ethyl-SH-isoxazolol 5,4-d lpyrimidin-4-one 3-Ethyl-6-( l-methylpropyl )-5H-isoxazolo[ 5,4-d1pyrimidin- 4-one 3-Ethyl-6-(2-methylpropyl)-5l-l-isoxazolo[5,4-d1pyrimidin- 4-one 6-Cyclopentyl-3-isopropyl-SH-isoxazolo[5,4-dlpyrimidin- 4-one 3-Propyl-6-trifluoromethyl-SH-isoxazolo[5,4-d]pyrimidin- 4-one 3-Ethyl-6-propyl-5l-l-isoxazolo[5,4-d1pyrimidin-4-one 3,6Dirnethyl-5H-isoxazolo[5,4-d1pyrimidin-4-one 6-Ethyl-3-propyl-5H-isoxazolo[5,4-d]pyrimidin-4-one Of the metallic and amine salts of my new isoxazolopyrimidines, I prefer the sodium and amine salts as they appear to manifest superior herbicidal activity.

It will be appreciated that my new isoxazolopyrimidines are potentially capable of existing in three forms, viz.:

0 V OH The preparation of my new isoxazolopyrimidines may be conveniently carried out from readily available material in a straightforward manner. Methods thereof are illustrated by situation. the following schema wherein R and R have the significance Other members of my new class of isoxazolopyrimidines set forth therefor above:

CN RC(OR"); HINGE R CN RC=C 1 HzC(CN)2 v \O NH,

ac latin EE/ lagznt g I v acylating NH CN I NHI agent L 1H2C\ 0 o N C-NHz NHlOH R m Ill T \o/-N=(l]0R O RC(OR) 0N R ia -01v R--C= J I ON 6R C ORIII TNHZ H2O Inorder that my invention may be readily available to those a skilled in the art, specificexamples of the preparation of a number of my new isoxazolopyrimidines, following a brief description of the preparation of intermediates that may be conveniently used therefor, are given:

Synthesis of Intermediate Alkenonitriles The method described by Taylor and Garcia (J. Org. Chem. 29, 2116 1964)) was employed for reaction of malononitrile with the appropriate trialkyl orthoalkanoate to give the corresponding Z-cyano-3-alkoxy-2-alkenonitrile, the structure of which was verified by infrared or NMR spectral analysis:

I 2 cyano-3-methoxy-2-butenonitrile, b.p. l ll 24 v Z-cyano-3-ethoxy-2-pentenonitrile, b.p. 788 l/0.02mm; 2-cyano-3-ethoxy-2-hexenonitrile; b.p. 1 54-1 8"] 1 2mm; 2-cyano-3-methoxy-Z-heptenonitrile, b.p. 9095/0.06mm; 2-cyano-3-ethoxy-4-methyl-Z-pentenonitrile, b.p. 1 l8-135 /12mm. Synthesis of Intermediate, 5-amino-4-cya'no-3-alkylisoxazoles A. From 2-cyano-3-alkoxy-2-a1kenonitriles Using the method employed by Taylor and Garcia (loc. cit.) for the corresponding 3-ethylisoxazole, the appropriate 2- cyano-3-alkoxy-2-alkenonitrile was reacted with hydroxylarnine to give the corresponding 5-amino-4-cyano-3-alkylisoxazole, the structure of which was verified by infrared 0 NMR analysis:

5-amino-4-cyano-3-ethylisoxazole, m.p. 140-142;

5-amino-4-cyano-3-methylisoxazole, m.p. 195-200; 5-amino-4-cyano-3 propylisoxazole, m.p. l 20-1 22; 5-amino-4-cyano-3 isopropylisoxazole, m.p. 125-128; 5-amino-3-butyl-4-cyanoisoxazole, m.p. 126-128.5; 5-amino-3-tert-butyl-4-cyanoisoxazole, m.p. 176-178.

B. From malononitrile To a chilled (0-] 0) mixture of 2.4 g of sodium hydride and 6.6 g of malononitrile in 125 ml of ethanol was slowly added a cold solution of l-chlorotrimethylacetaldoxime (freshly prepared by chlorination of g of trimethylacetaldoxime) in 25 ml of ethanol. The mixture was allowed to stand at ca 0 for 60 hours. The, dark mixture was then filtered and the filtrate concentrated to give a dark brown semisolid. The semisolid was taken up in ethanol, the solution was treated with activated charcoal and from the solution was obtained 4.6 g of 5- amino-3-tert-butyl-4-cyanoisoxazole, m.p. l 76-178.

Analysis: Calcd for CJl NQO: C 58.17; H 6.71; N 25.44; I

Found:'C 58.70; H 7.15; N 24.92. Synthesis of Intermediate, 5-amino-3-alkylisoxazole-4-carboxamides i r A. By hydrolysis of 5-amino-4-cyano-3-alkylisoxazoles Using the method of Taylor and Garcia (loc. cit.), the appropriate 5-amino-4-cyano-3-alkylisoxazo1e was hydrolyzed by reaction with concentrated sulfuric acid to give the cor responding 4'-carboxamide:

5-amino-3-methylisoxazole-4-carboxamide, m.p. l85 190 S-amino-3-ethylisoxazole-4-carboxamide, m.p. l95-l 97".

8. From 2-cyanoacetamidez vA suspension of 72 g of sodium hydride in l,200 m1 of dimethylformamide was cooled to and to it was slowly added, with stirring, 252.3 g of cyanoacetamide', the rate of addition being regulated so as to control foaming. The mixture was then cooled to --40 where it was maintained while'to it was slowly added a chilled (20) solution of freshly prepared (by reaction of 212 g of chlorine with 261.4 g of isobutyral doxime'in'Z liters of ice water) l-chloroisobutyraldoxime in 900 ml of methylene chloride. The mixture was stirred at 40 to '-70 for ca 18 hours, then allowed to wann slowly to room temperature during 24 hours. The mixture was concentrated (reduced pressure) to one-third volume and poured into ice. The solid was collected by filtration and dried to give 255 g of 5-amino-3-isopropylisoxazole 4-carboxamide, m.p. l79-l82 I; The method of Rajagopalan and Talaty (Tetrahedron 23,

' dIpyrimidin-4-one, m.p. l70-174. Recrystallization from EXAMPLE I 6-tert-Butyl-3-methy1-5H-isoxazolo[5,4-d]pyrimidin-4-one A mixture of 10 g of 5-amino-4-cyano-3-methylisoxazole (m.p. 195-200, prepared according to the method of Taylor and Garcia, J. Org. Chem. 29, 2116 (1964)), 20 ml of trimethylacetic anhydride and 4 ml of concentrated sulfuric acid was heated for 2 hours at 100. The mixture was poured EXAMPLE ll 3,6-Diethyl-5H-isoxazolo[ 5 ,4-d]pyrimidin-4-one A mixture of 9.8 g of S-aminc-3-ethylisoxazole-4-carboxamide (m.p. l95-l97, preparedaccording to the method of Taylor and'Garcia', loc. cit.), 75 ml of acetic anhydride and 75 ml of triethyl orthopropionate was heated under reflux for 5 hours. Volatile material was removed by heating'(hot water bath) under reduced pressure and the residue dissolved in ammonium hydroxide. The basic solution was treated with activated carbon and the filtered solution acidified to pH'5-6 with acetic acid. The acidic solution was chilled for several hours and the precipitate collectedto obtain, after recrystallization from ethanol, 5.3 g of 3,5-diethyl-5H-isoxazolo[5,4-

ethanol increased the melting point to l74-l 75.

2 Analysis: Calc'd for C,H N,O,: C 55.95; H 5.74; N 21.75;

Found: c 55.84; it 5.82; N 21.78.

EXAMPLE m 3-Ethyl-6-methyl-5H-isoxazolo[5,4-d1pyrirnidin-4-one A mixture of 10 g of 5-amino-3-ethylisoxazole-4-carboxamide (m.p. 198-200), 25 ml of triethyl orthoacetate and 75 ml of acetic anhydride was heated under reflux for 20 hours.

' The mixture was processed as described in Example 11 to give 8.1 g of 3-ethyl-6-methyl-5H-isoxazolol5,4d]pyrimidin-4- one, m.p. ,233-235.. Analysis: Calcd for C,H.N,O,: C 53.63; H 5.06; N 23.45;

Found: C 53.64; H 5.21; N 23.21.

EXAMPLE lV 3-Ethy1-6-isopropyl- 5H-isoxazolol5,4-d1pyrimidin-4-one A mixture of 10 g of 5-amino-3-ethylisoxazole-4-carboxamide, 25 ml of triethyl orthoisobutyrate and 30 ml of acetic anhydride was treated under reflux for 3 hours. The residue remaining after removal of volatile materials was soluble in ammonium hydroxide only with difficulty. Acidification of the Y solution yielded a precipitate which was shown by infrared and NMR analyses to be the same as the undissolved material. The yield was 2.5 g. Recrystallization from ethanol-pentane gave pure 3-ethyl-6-isopropyl-5H-isoxazolo[5,4-d1pyrimidin- Analysis: Calcd for C l-l N,O,: C 57.96; H 6.32; N 20.28;

Found: C 57.46; H 6.31; N 20.23.

EXAMPLE v 6-Butyl-3-ethyl-5H-isoxazolo[5 ,4-d]pyrimidin-4-one A mixture of 10 g of 5-amino-3-ethylisoxazole-4-carboxamide, 25 ml of triethyl orthovalerate and 75 ml of acetic an- EXAMPLE VI EXAMPLE Vlll 3-Ethyl-6-( l-methylpropyl)-5l-l-isoxazolo[5,4-d]pyrimidin-4- one Using the procedure of Example V1, 10 g of 5-amino-4- cyano-3-ethylisoxazole and ml of 2-methylbutyric anhydride were reacted in the presence of 10 ml of fuming sulfuric acid to give, after recrystallization from ethanol-water,

of 3-ethyl-6-( 1-methylpropyl)-5H-isoxazolo[ 5,4- dlpyrimidin-4-one, m.p. 90-92. Analysis: Calcd for C ,H, N O C 59.71; H 6.83; N 18.99;

Found: C 59.32;l-1 6.79; N 18.35.

EXAMPLE IX 3-Ethyl-6-tert-butyl-5H-isoxazolo[5,4-d]pyrimidin-4-one A mixture of 18.7 g of 5-amino-3-ethylisoxazole-4-carboxa- A mide and 40 ml of pivalic anhydride was cooled to 5. To the cold mixture was slowly added with stirring 8 ml of concentrated sulfuric acid, maintaining the temperature below 10. The mixture was then heated to 150 where it was maintained for 0.5 hour. The two layers present were separated by decantation. The lower layer was poured into 200 ml ice water. The solid which separated was found to be unreacted 5-amino-3- ethylisoxazole-4-carboxamide. The upper layer was poured into 150 ml of ice water and the aqueous mixture was extracted with ethyl ether. Since an ether-insoluble solid was present, the ether layer was decanted and the aqueous layer filtered to give a solid, m.p. 205-206. The volatile materials were removed under reduced pressure to leave a solid, m.p. 205-206, which was shown by NMR analysis to be identical with the previous solid. The combined yield was 2.8 g of 3- ethyl-6-tert-butyl-5H-isoxazolo[5,4-d]pyrimidin-4-one. Analysis: Calc'd for c,,H,,N .,o, C 59.71; H 6.83; N 18.99;

Found: C 59.98; H 7.10; N 18.78.

EXAMPLE X 3-tert-Butyl-6-methyl-5H-isoxazolo[5,4-d]pyrimidin-4-one Using the method of Example IV, 5.1 g of 5-amino-3-tertbutylisoxazole-4-carboxamide (m.p. 149.5l50, prepared according to the method of Rajagopalan and Talaty, Tetrahedron, 23, 3541 (1967)) and 10 ml of acetic anhydride were reacted in the presence of 2 ml of concentrated sulfuric 70 acid. The entire reaction mixture was poured into 100 ml of crushed ice, stirred until the ice had melted and filtered while still cold. The solid obtained was recrystallized from methanol to give 4.0 g of 3-tert-butyl-6-methyl-5H-isoxazolo[5,4-d] pyrimidin-4-one, m.p. 244246. Analysis: Calcd for o l-1. 14 0 C 57.96; H 6.32; N 20.28;

Found: C 57.25; H 6.80; N 20.33.

EXAMPLE X1 3-tert Butyl-6-propyl-5H-isoxazolo[5,4-d]pyrimidin4-one Employing the method of Example X, 5.1 g of 5-amino-3- tert-butylisoxazole-4-carboxamide and 10 ml of butyric anhydride were reacted in the presence of 2 ml of concentrated sulfuric acid to give, after recrystallization from methanol, 5.0 g of 3-tert-butyl-6-propyl-5H-isoxazolo[5,4-d]pyrimidin-4- one, m.p. l68l70. Analysis: Calc'd for C,,H N,,O,: C 61.26; H 7.28; N 17.86;

Found: C 60.96; H 7.54; N 17.75.

EXAMPLE Xll 3,6-Dimethyl-5H-isoxazolol5,4-d]pyrimidin-4-one A. Ethyl 2-cyano-3-ethoxy-2butenoate A mixture of g of ethyl cyanoacetate and 143.2 g of triethyl orthoacetate was heated under reflux for 18 hours and the mixture distilled under reduced pressure. After removing volatiles distilling at temperature below under 21 mm, the product was collected at l03-l05 under 0.12 mm, m.p. 67-70. Recrystallization from ethyl ether-pentane gave 78 g of ethyl 2-cyano-3-ethoxy-2-butenoate, m.p. 70-72. Analysis: Calcd for C H, NO C 59.00; H 7.15; N 7.65;

Found: C 58.83; H 7.18; N 7.77.

B. Ethyl 5-amino-3-methy1isoxazole-4-carboxylate A solution of 74 g of ethyl 2-cyano-3-ethoxy-2-butenoate in 200 ml of ethanol was added slowly, maintaining the temperature below 50, to a solution of 23 g of hydroxylamine hydrochloride and 45 g of sodium acetate in 200 ml of water. The mixture was stirred for 18 hours (temperature throughout below 50), then chilled. The solid which separated was collected by filtration (38 g') and the mixture again chilled and filtered (16.6 g). The solids were combined and recrystallized from benzene to give 43.3 g of ethyl 5-amino-3-methylisoxazole-4-carboxylate, m.p. l33135. Analysis: .Calcd for C-,H, N O C 49.41; H 5.92; N 16.46;

C. Ethyl 5-[(l-met.hoxyethylidene)amino]-3-methyl-isoxazole-4-carboxylate A reflux apparatus was set up and purged with dry nitrogen gas, then into it was introduced 29.9 g of ethyl 5-amino-3- methylisoxazole-4-ca.rboxylate and a solution of 68.5 g of trimethyl orthoacetate in 75 m1 of acetic anhydride. The mixture was heated at reflux under a nitrogen atmosphere for 4 hours, then concentrated under reduced pressure to give 38 g of a solid which melted below room temperature. This product was used without further purification.

D. 3,6-Dimethyl-5H-isoxazolo[ 5,4-d]pyrimidin-4-one A mixture of 38 g of ethyl 5-[(1-methoxyethylidene)- amino]-3-methylisoxazole-4-carboxylate and 50 ml of concentrated ammonium hydroxide was heated under reflux for 3 hours. The mixture was cooled, filtered and the filtrate was treated with activated carbon. The decolorized filtrate was made acid by addition of acetic acid and the acidic suspension chilled for several hours. The solid precipitate was collected on a filter and washed with water to give 1.7 g of 3,6 dimethyl- 5H-isoxaz0lo-[5,4-d]pyrimidin-4-one, m.p. 273-278. Analysis: Calc'd for C,l-l-,N O C 50.91; H 4.27; N 25.44;

Found: C 51.03; H 4.21; N 25.48.

EXAMPLE Xlll dried to give 3.8 g of 6ethyl-3-propyl-5H-isoxazolo[5,4-d]

pyrimidin-4-one, m.p. 156l 58. Recrystallization from ethanol-water 1:3) increased the melting point to 158-1 60.

Analysis: Calcd for C, H ,N,O,: C 57.96; H 6.32; N 20.28;

Found: C 57.76; H 6.51; N 20.39.

EXAMPLE XIV EXAMPLE XV 6-Isopropyl-3-propyl-5H-isoxazolo[5,4-d]pyrimidin-4-one Using the method of Example XIII, 6 g of -amino-4-cyano- 3-propylisoxazole and 18 m1 of isobutyric anhydride reacted to give 3' g of 6-isopropyl-3propyl-5H-isoxazolo[5,4-d] pyrimidin-4-one, m.p. 151l52 (after recrystallization from ethanol-water). Analysis: Calcd for c,,ri.,N,o.: C 59.71; H 6.83; N 18.99;

Found: C 59.93; H 6.68; N 19.14.

EXAMPLE XVI 3-Propyl-6-trifluoromethyl-5-H-isoxazolo[5,4-d]pyrimidin-4- one Using the method of Example XIII, g of 5-amino-4- cyano'-3-propylisoxazole and 30 ml of trifluoroacetic anhydride reacted to give 9.5 g of 3-propy1-6-trifluoromethyl-5 H-isoxazolo-[S,4-d]pyrimidin-4-one, m.p. 173l 75. The two reactants in this case formed a solid which went into solution only after the mixture with sulfuric acid was heated.

Analysis: Calcd for cgmFaNgogi C 43.73; H 3.26; F 23.06; N 17.00;

Found: C 42.65; H 3.09; F 23.66; N 17.72.

EXAMPLE XVII Using the procedure of Example IX, except that the mixture was heated on a steam bath for 1 hour, 9.9 g of 5-amino-3- butyl-4-cyanoisoxazole and 20 ml of propionic anhydride were reacted to give 8.6 g of 3-butyl-6-ethyl-5H-isoxazolo[5,4-d1-pyrimidin-4-one, m.p. l49-150.' Analysis: Calc'd for C H 5N,O,: C 59.71; H 6.83; N 18.99;

Found: C 59.74; H 6.69; N 18.92.

. EXAMPLE XVlll 6-Cyclopropyl-3-propy1-5H-isoxazolo[5,4-d1pyrimidin-4-one 1A mixture of 27.7 g of trifluoroacetic anhydride, 1 1.4 g of cyclopropane carboxylic acid and 10 ml of sulfuric acid was stirred for 0.5 hour at 50. To the stirring mixture was then added 10 g of 5-amino-4-cyano-3-propylisoxazo1e and the mixture was heated on a steam bath for 1.25 hours. The hot mixture was poured into 150 ml of ice and stirred until the ice had melted. The water layer was decanted and the heavy semisolid recrystallized from ethanol to give 1.9 g of 6- cyclopropyl-propyl-S H-isoxazolo[ 5 ,4-d]pyrimidin-4-one m.p. 21 1-214. Recrystallization again from ethanol increased the melting point to 2152l6. Analysis: Calc'd for C, l-I,,N,O,: C 60.26; H 5.98; N 19.17;

Found: C 60.01; H 6.60; N 19.82. 1

EXAMPLE XIX 6-Ethyl-3-isopropyl-5H-isoxazolo[5,4-dlpyrimidin-4-one EXAMPLE xx 3,6-Diisopropyl-5 H-isoxazolo[ 5,4-d Jpyrimidin-4-one Using the method of Example XIX, 4 g of 5-amino-4-cyano- 3-isopropylisoxaxole and 12 ml of isobutyric anhydride were reacted in the presence of 4 ml of concentrated sulfuric acid to give 1.2 g of 3,6-diisopropyl-5H-isoxazolo[5,4-d]pyrimidin- 4-one, m.p. 162-l 64. Analysis: Calcd for C l-I N,O,: C 59.71; H 6.83; N 18.99;

Found: C 58.85; H 6.95; N 19.20.

EXAMPLE xxl 6-Cyclopentyl-3-isopropyl-5H-isoxazolo[5,4-djpyrimidin-4- one Using the method of Example XIX, 25 g of 5-'amino-3- isopropylisoxazole-4-carboxamide and 50 ml of cyclopen tane carboxylic anhydride were reacted in the presence of 7 ml of concentrated sulfuric acid to give, after recrystallization from ethanol, 13.0 g of 6-cyc1opentyl-3-isopropy1-5H-isoxazolo[5,4-d]-pyrimidin-4-one, m.p. 182184. Analysis: Calc'd for C,,H,,N,O,: C 63.14; H 6.93; N 16.99;

Found: C 63.50; H 7.00; N 17.24.

EXAMPLE XXII 3-lsopropyl-6-methyl-5 l-I-isoxazolo[5,4-d1pyrimidin-4-one Using the procedure of Example XIX, 7.5 g of 5-amino-3- isopropylisoxazole-4-carboxarnide and 15 ml of acetic anhydride were reacted in the presence of 3 ml of concentrated sulfuric acid to give, after recrystallization from ethanol, 5.1 g

of 3-isopropyl-6-methyl-5H-isoxazolo[5,4-d]pyrimidin-4-one,

m.p. 191l93. Analysis: Calc'd for C,H N,O,: C 55.95; H 5.74; N 21.75;

Found: C 55.97; H 5.64; N 22.11.

EXAMPLE XXIII 6-tert-Butyl-3-isopropyl-5H-isoxazolo[5,4-d1pyrimidin-4-one A mixture of 7.5 g of 5-amino-3-isopropylisoxazole-4-carboxamide, 15 ml of trimethylacetic anhydride and 4.5 ml of sulfuric acid was heated for 1.5 hours on a steam bath. Two liquid phases were present. The upper layer, consisting of trimethylacetic acid, was decanted and the lower layer poured onto ice..'l'he water was decanted, the semisolid mass dissolved in ethanol and the solution treated with activated carbon. From the solution was obtained 1.2 g of 6-tert-butyl-3- isopropy1-5H-isoxazolo[5,4-d]pyrimidin-4-one, m.p. 227-22 9 Analysis: Calc'd for C,,H N,O,: C 61.26; H 7.28; N 17.86;

Found: C 61.02; H 7.52; N 18.08.

EXAMPLE XXIV 3-tert-Butyl-6-ethyl-SH-isoxazolol5,4-d1pyrimidin-4-one A mixture of 4.6 g of 5-amino3-tert-butyl-4-cyanoisoxazole I and 10 ml of propionic anhydride was cooled to 5 and to it was slowly added, maintaining the temperature at 5, 5 ml of concentrated sulfuric acid. The mixture was stirred for 15 minutes at 5, then heated on the steam bath for 1 hour. The

mixture was poured onto ice to give a solid which was taken' up in ethanol and the solution was treated with activated carbon. From the solution was obtained 3.1 g of 3-tert-butyl-6- ethyl-5H-isoxazolo[5,4-d]pyrimidin-4-one m.p. 191-l 93.

Analysis: Calcd for C,,H,,N,O,: C 59.71; H 6.83; N 18.99;

Found: C 60.00; H 7.08; N 19.09.

EXAMPLE XXV 3-tert-Butyl-6-isopropyl-5H-isoxazolo[5,4-d]'pyrimidin-4-one Using the procedureof Example XlX, 6.5 g of 5-amino-3- tert-butyl-4-cyanoisoxazole was reacted with 12 ml of isobutyric anhydride in the presence of 6 ml of fuming sulfuric acid to give, after two recrystallizations from ethanol, 1.3 g of 3- EXAMPLE XXVI 6-tert-Butyl-3-propyl-5l-l-isoxazolo[5,4-d]pyrimidin-4-one Using the procedure of Example XIX, 10 g of 5-amino-4- cyano-3-propylisoxazole and 20 ml of trimethylacetic anhydride were reacted in the presence of 4 ml of concentrated sulfuric acid to give, after recrystallization from ethanol, 3.3 g of 6-tert-butyl-3-propyl-5H-isoxazolo[ 5 ,4-d ]pyrimidin-4-one m.p. l70-1 72. Analysis: Calcd for C I-1 N C 61.26; H 7.28; N 17.86;

Found: C 61.59; H 7.41; N 18.00.

EXAMPLE XXVll 6-Ethyl-3-methyl-5H-isoxazolo['5,4-d1pyrimidin-4-one Using the method of Example 1, 89.9 g of -amino-3- methylisoxazole-4-carboxamide, 229 g of triethyl orthopropionate and 640 ml of acetic anhydride were refluxed for ca 18 hours. After removal of volatile materials, the product was dissolved in hot ammonium hydroxide, treated with activated carbon, filtered and the filtrate acidified to give 50 g of 6-ethyl-3-methyl-5l-l-isoxazolo[5,4-dlpyrimidin-4-one, m.p. 252-254, which on recrystallization from ethanol melted at 254-255. Analysis: Calccl for C H N O C 53.63; H 5.06; N 23.45;

Found: C 52.79; H 5.00; N 23.46.

To demonstrate the biological activity of the compounds provided by this invention, they were screened in standard herbicidal tests according to the following methods and with the following results:

Preemergence Herbicidal Tests 1. Initial Screening Test crop seeds were planted in shallow flat-bed trays containing 2 to 3 inches of a loam soil. Within 24 hours after planting an aqueous-acetone solution of the candidate herbicide was sprayed on the soil at a rate of 8 pounds active ingredient per acre. Test plants were maintained in a greenhouse and watered regularly for 2 weeks, after which time the phytotoxicity of the candidate herbicide was recorded. In-- dividual plant species were examined for percent kill, and a vigor rating of one to five was assigned to the surviving members of the species, a vigor rating of five signifying no chemical injury. Untreated control plants were maintained in every test carried out.

2. Primary Evaluation Using the same test species and procedures utilized in initial screening tests, the candidate herbicide was evaluated for preemergence activity at a rate of 8 pounds per acre and submultiples thereof (i.e., 4 pounds per acre, 2 pounds per acre, etc.).

3. Secondary Evaluation Following the procedure utilized in initial screening tests, an aqueous-acetone solution of the candidate herbicide was sprayed on the soil surface of flat-bed trays in which had been planted additional plant species. Candidate herbicides were applied at 8 pounds per acre and submultiple rates. In soil-incorporation evaluations the candidate herbicide was thoroughly mixed in the upper profile of the soil. The growth trays were maintained in a greenhouse forca two weeks after which time, per cent kill and vigor ratings of each species were recorded.

Tables 1 A-C list results of preemergence herbicidal testing:

TABLE I A Preemergence l-lerbicidal Screening of 3,6-

Diethyl-Sl-Lisoxazolo[5,4-d]pyrimidin-4-one Test Plant Species Vigor Kill Lima beans 1 40 Corn 2 0 Lettuce 100 Mustard 100 Crabgrass 100 i M LL TABLEIB Preemergence Primary Evaluation of Compounds n-4-one 8.0lb/acre Test plant vigor kill vigor kill vig 'or kill vigor kill vigor kill Species Lima beans 5 0 4 0 l 2 80 100 Dent corn 4 0 3 0 l 0 l 0 60 Lettuce 4 0 3 40 1 l Mustard 2 90 l 100 100 100 Crabgrass 3 0 3 60 l 95 100 100 3-Ethyl-6isopropyl-5l-l-isoxazolo[ 5,4-d

]pyrimidin-4-one Lima beans 3 0 2 60 100 100 I00 Dent corn 3 0 3 20 2 60 l 80 80 Lettuce 4 0 3 50 100 100 100 Mustard 3 90 100 100 11 100 100 Crabgrass 3 50 100 100 100 100 3-Ethyl-6-methyl-5 l-l-isoxazoloI 5,4-d

]pyn'midin-4-one Lima beans 4 O 4 0 4 0 2 0 0 Dent corn 5 0 4 0 2 30 I00 100 Lettuc'e 5 0 5 O 4 0 2 20 80 Mustard 5 O 5 0 3 30 l 80 95 Crabgrass 5 0 4 0 3 0 3 20 95 3,6-Diisopropyl-5H-isoxazolo[5,4-

dlpyn'midin-4-one Lima 1 60 100 100 100 100 beans Dent 4 0 3 0 3 60 100 100 com Lettuce 100 100 100 100 100 Mustard 100 100 100 100 100 Crab- 100 100 100 100 100 grass 6-Ethyl-3-isopropyl-5l-l-isoxazolo[5,4-d

]pyrimidin-4-one Lima 1 80 100 100 100 100 beans Dent 2 20 3 0 1 40 100 100 com Lettuce 100 100 100 100 100 Mustard 100 100 100 100 100 Crab- 100 100 100 100 I00 grass 6-lsopropyl-B-propyI-Sl-l-isoxazolcl 5,4-d

]pyrimidin-4-one Lima 100 100 100 100 100 beans Dent 3 0 3 0 2 0 1 20 40 com Lettuce 100 100 l00 I00 100 Mustard 100 3 50 I00 100 100 Crab- 3 60 3 60 100 100 I00 grass 6-Ethyl-3-methyl-Sl-l-isoxazolol 5 ,4-d

]pyrimidin-4-one Lima 5 v 0 5 0 3 0 3 20 60 beans Dent 4 0 4 0 3 0 2 60 80 corn Lettuce 5 0 4 0 3 50 2 90 100 Mustard 5 0 3 80 100 100 I00 Crab- 5 0 4 0 3 70 100 100 grass 3-Butyl-6-ethyl-5 H-isoxazoloI 5 ,4-d1pyrimidin- 4-one Lima 5 0 4 0 3 20 3 60 100; beans Dent 5 0 4 0 4 0 3 0 50 com Lettuce 4 0 3 0 3 40 100 I00 Mustard 4 0 4 0 3 70 100 100 Crab- 5 0 4 0 3 80 100 100 grass 3-tert-Butyl-6-ethyl-SH-isoxazolo[5,4-d

]pyrimidin-4-one Lima 100 I00 100 100 100 beans Dent 2 20 2 20 l 40 100 100 com yard grass Cotton I 3 80 100 I00 I00 Tomato I00 100 I00 I00 I00 Rice 100 3 95 I00 I00 100 Safflower I 95 3 30 I00 I00 100 Red clover I00 100 I00 I00 100 Sugar beets 100 I00 I00 I00 I00 Wild cats 2 80 3 80 I00 I 00 l 00 Soybeans 3 40 3 20 I00 I00 I00 Wheat 3 40 2 60 100 I00 I00 Postemergence Herbicidal Tests 1. Initial Screening Test crop seeds were planted in shallow flat-bed trays containing 2 to 3 inches of a loam soil. The growth trays were maintained in a greenhouse and regularly watered for approximately 2 weeks. When the first trifoliate leaves of bean plants were unfolding, the test plants were removed from the greenhouse and sprayed with an aqueous-acetone solution of the candidate herbicide at a rate of 8 pounds active ingredient per acre. The plants were maintained in the greenhouse and watered regularly for an additional two weeks, after which time the phytotoxicity of the candidate herbicide was recorded. Individual plant species were examined for per cent kill, and a vigor rating of one to five was recorded for surviving members of the species, a vigor rating of five signifying no chemical injury. Untreated control plants were maintained in every test carried out.

2. Primary Evaluation Using the same test species and procedures utilized in llllflal' screening tests, the candidate herbicide was evaluated for postemergence activity at a rate of 8 pounds per acre and submultiples thereof (i.e., 4 lbs/acre, 2 lbs/acre, etc.).

3. Secondary Evaluation Following the procedure utilized in initial screening tests, an aqueous-acetone solution of the candidate herbicide was sprayed on a large number of plant species which had been grown for about 2 weeks in flat-bed trays. Candidate herbicides were applied at 8 pounds per acre, and submultiple rates. Plants were maintained in a greenhouse for approximately an additional two weeks, after which time, per cent kill and vigor ratings of each species were recorded.

Tables I D-F list results of postemergence herbicidal testing:

TABLE] D Postemergence Herbicidal Screening 3,6-DiethyI-5H-isoxazolo [5,4-d1pyrimidin-4-one Test Plant Species Vigor Lima beans 100 Dent corn 2 0 Lettuce 100 Mustard 100 Crabgrass 100 3-Ethyl-6-isopropyl-5l-l-isoxazolo [5 ,4-dlpy Lima beans 00 Dent corn I 60 Lettuce 100 Mustard 100 Crabgrass 100 3-Ethyl-6-methyl5H-isoxaz0lo [5,4-d1pyrimidin-4-one Lima beans 100 Dent corn 3 0 Lettuce 100 Mustard 100 Crabgrass I 95 6-Ethyl-3-methyl-5l-l-isoxazolo [5,4-d1pyrimidin-4-one Lima beans 100 Dent corn 2 o Lettuce 100 Mustard 7 100 Crabgrass 2 50 6-Butyl-3-ethyl-5l-l-isoxazolol 5,4-d1pyrimidin-4-one Lima beans 100 Dent corn 3 20 Lettuce 100 Mustard 100 Dent l4 Crabgrass 3 90 3,6-Dimethyl-5H-isoxazolo[5.4 -d]pyrimidin-4-onc Lima beans 20 Dent corn 3 O Lettuce I00 5 Mustard I00 Crabgrass 3 10 TABLE I E Postemergence Primary Evaluation 3,6-Diethyl-5 H-isoxazolol 5,4- d lpyrimidin-4-onc Test 0.5lb/acre I.0lblacre 2.0lblacre 4.0Ib/acre 8.0lb/ucrc Plant l b i: k k Spevigor kill vigor kill vigor kill vigor kill vigor kill ones Lima beans I00 I00 I00 I00 100 Dent corn 5 0 3 0 2 0 I00 I00 Lettuce 100 100 I00 I00 I00 Mustard 100 100 100 100 100 Crab grass I00 I00 I00 I00 100 3-Ethyl-6-isopropyI-5 H-isoxazolo [5,4-d1pyrimidin- 4-one Lima beans I00 I00 I00 I00 I00 Dent corn 3 0 TI 3 0 I00 I00 I00 Lettuce 100 I00 I00 100 I00 Mustard I00 I00 I00 100 100 Crabgrass I00 I00 I00 I00 I00 3,6-Diisopropyl-5H-isoxazolo[ 5,4-dlpyrimidin-4-one Lima beans I00 100 100 I00 I00 Dent corn 3 0 2 0 2 50 I00 I00 Lettuce 100 100 I00 I00 100 Mustard I00 100 I00 I00 I00 Crabgrass I00 I00 I00 100 I00 I6:Ethyl-3-isopropyl-5 l-l-isoxazolo 5,4-d1pyrimidin-4-one rma beans 100 I00 100 I00 100 Dent com 3 0 2 0 2 0 I00 I00 Lettuce 100 100 I00 100 100 Mustard I00 I00 100 I00 I00 Crabgrass 100 100 I00 I00 I 00 6-lsopropyl-3-propyl-5l-l-isoxazolo [5,4-dlpyrimidin-4-one Lima beans 100 I00 100 I00 100 Dent corn 3 0 2 0 l 80 100 I00 Lettuce I00 I00 100 I00 I00 Mustard 100 I00 I00 I00 I00 Crab- 5O grass 100 I00 I00 I00 I00 i- Butyl-6-ethyl-5l-l-isoxazolo[ 5,4-d1pyrimidin-4-one [m3 beans 3 0 3. 0 I00 I00 I00 Dent corn 4 0 3 0 2 0 2 20 2 20 Lettuce I00 I00 100 I00 I00 Mustard 3 40 3 80 I00 I 00 I 00 Crabgrass 3 v 0 3 l0 3 10 I00 I00 ilftert-Butyl-6-ethyl-SH-isoxazolo [5,4-d]pyrimidin-4-one ms beans I00 I00 100 I00 I00 Dent corn 2 0 2 0 2 40 2 80 2 80 Lettuce I00 I00 I00 I00 I O0 Mustard I00 100 100 I00 I00 Crabgrass 2 90 100 I00 I00 I00 3-tert-Butyl-6-isopropyl-Sl-l-isoxazolo[ 5,4-dlpyrimidin- 4-one Lima beans 2 80 100 I00 I00 Dent corn 3 0 2 0 2 80 I00 Lettuce I00 I00 I00 100 Mustard 100 100 I00 I00 Crabgras 3 20 3 40 40 2 6-tert-Butyl-3-isopropyl-SH-isoxazolo[ 5,4-d1pyrimidin- 4-one Lima 75 beans 3 so 2 15 100 Y QQ v 3-Ethyl-6-propyI-5I-I-isoxazolo corn 5 0 0 2 0 Lettuce I00 I00 I00 I00 Mustard I00 I00 I00 I 00 Crabgrass 3 50 2 50 I00 I00 6-Cyclopropyl-3-pr0pyl-5H-isoxazolo[ 5, 4-dlpyrimidincom50403 0202 Lettuce I00 I00 I00 I00 Mustard I00 I00 I00 I00 Crabrass 4 0 4 0 2 95 I00 -tertButyl-6-propyl-5H-isoxazolo [5,4-d lpyrimidin-4- one Lima

beans 4 0 3 0 3 0 I00 Dent corn 5 0 4 0 4 0 2 O 2 Lettuce 3 30 3 30 I 90 I00 Mustard 4 0 3 30 2 70 I00 Crabgrass 5 0 4 0 3 I0 3 60 din-4-one I Lima beans 3 0 I 80 I00 I00 Dent I I com 5 0 4 0 3 0 2 6O 2 Lettuce I00 I00 I00 I00 Mustard 3 40 100 I 00 I00 Crab- 0 grass 4 0 4 0 3 I0 I00 3-E thyI-6-(2-methyIpropyI)-5l-I -isoxazolo[ 5,4-d]pyrimiv I din-4-one Lima I beans 3 0 3 0 2 0 I 80 Dent 1 corn 5 0 4 0 4 0 3 0 2 Lettuce 3 I0 3 70 2 80 I00 Mustard 3 20 3 80v I 90 I00 Crab- 6-Cyclopentyl-3-isopropyl-5H- din-4-one Lima beans 5 0 S 0 4 -0 3 0 3 Dent I corn 5 0 5 0 5 0 4 0 4 Lettuce 4 I0 3 60 3 80 3 80 3 vMustard 4 0 3 20 I00 3 80 2 Crabgrass 5 0 5 0 4 0 3 3 0 [5,4-d1pyr-imidin-4-one Lima beans 4 0 3 0 3 40 I00 Dent corn 5 0 5 0 4' 0. 3 0 2 I Lettuce 3 70 I00 I00 I00 Mustard 3 70 3 70 I00 I00 Crab- I grass 5 0 4 0 4 IO 3 70 2 6Ethyl-3-propyl-SH-isoxazolo [5,4-dlpyrirnidin-4-one Lima beans I00 I00 I00 I00 Dent v I corn 3 0 3 20 2 50 l 60 Lettuce I00 100 I00 I00 Mustard I00 I00 I00 I00 Crab- I grass I00 I00 I00 I00 34ert-Butyl-6-Methyl-SlI-isoxazolo [5,4-d1pyrimidin- 4-one Lima beans 3 I00 I00 I00 Dent com 4 0 4 0, 4 0 3 0 2 Lettuce I00 I00 I00 I00 Mustard I00 I00 I00 I00 Crab grass 3 3 50 3 60 I00 6- Methyl-3-propyI-5I-I-isoxazolo [5,4 dlpyrimidin-4-one grass 3 2o 3 2o 3 20 mo 10o 3 PropyI-6-trifluoromethyl-SI-I-isoxazolo[5,4-d1pyrimidin-4-one Lima beans 5 0 4 0 3 0 3 0 3 Dent corn 5 0 5 0 5 0 4 0 4 0 Lettuce I00 I00 I00 I00 I00 Mustard 5 0 3 70 I00 3 80 I00 Crabgrass 5 0 5 0 5 0 4 0 3 30 6-tert-Butyl-3-methyl-5H-isoxazolo 4-onc[5;4-d]pyrimidin-4-one Lima v beans 3 0 I00 I00 I00 I00 Dent corn 5 0 4 0 4 0 3 0 I00 Lettuce 3 30 3 60 I00 I00 I00 Mustard 3 30 I00 I00 I00 I00 Crabgrass 3 20 2 2 90 I00 I00 6- ert-ButyI-3-propyl-5H-isoxazolo 4-one[5,4-d]pyrimidin-4-one Lima beans I00 2 50 I00 I00 I00 Dent corn 3 0 4 0 3 0 3 0 2 70 Lettuce I00 I00 I00 I00 Mustard I00 I00 I00 I00 I00 Crabgrass 100 2 90 100 100 100 TABLE I F Postemergence Secondary Evaluation 3,6-Diethyl-5I-I-isoxazolo[5,4-d1pyrimidin-4-one Test 0.5lb/acre l .OIb/acre 2.0lb/acre 4t0lb/ acre 8.0lb/ acre Plant Species vigor kill vigor kill vigor kill vigor kill vigor kill Lima beans I00 2 80 I00 I00 I00 Dent corn 4 0 4 0 3 0 I 80 I I00 Lettuce I00 I00 I00 I00 I00 Mustard I00 I00 I00 I00 I00 Crab- I grass 1 3 60 3 80 I 60 I00 I00 Barnyard 1 grass. 4 80 I00 I00 I00 I00 Cotton I00 100 I00 I00 I00 Tomato I00 I00 I00 I00 I00 Rice 1100.. I00 I 100 I00 I00- Safflower I00 I00 I00 I00 I00 Red clover I00 I00 I00 I00 I00 Sugar beets I00 I00 I00 I00 100 Wild oats 3 60 I00 I00 100 I00 Soybeans 'l00 3 80 I00 I00 I00 I00 I00 I00 The preparation of easily usable compositions containing one or more of my new isoxazolopyrimidines may follow conventional procedures: I

' For herbicidal applications, the isox'azolopyrimidines of this invention are formulated by admixture; in herbicidally effective amounts, with the adjuvants and carriers normally employed for facilitating the dispersion of active ingredients for agricultural applications, recognizing that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, the compounds of this invention may be formulated as any of the several types of formulations well known to the herbicidal art, depending on the desired mode of application. Preferred formulations for both preand postemergence herbicidal applications are wettable- I 1 powders, emulsifiable concentrates, pastes and granules. These formulations may contain as little as 0.5 percent to as much as 95 percent or more by weight of active ingredient.

Typical carriers for wettable powders include fullers earth, kaolin clays, silicas and other readily wet organic or inorganic diluents. Wettable powders normally contain about 5-95 percent of active ingredient by weight and usually also contain a small amount of wetting, dispersing or emulsifying agent to facilitate wetting and dispersion. For example, a useful wettable powder formulation contains 80.8 parts by weight of the active isoxazolopyrimidin, 17.9 parts by weight of palmetto clay, and 1.0 part by weight of sodium lignosulfonate and 0.3 part by weight of sulfonated aliphatic polyester as wetting agents.

Emulsifiable concentrates may consist entirely of the active isoxazolopyrimidine either with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, and other non-volatile organic solvents. For herbicidal application these concentrates are dispersed in water or other liquid carrier, and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95 percent of active ingredient by weight of the herbicidal composition. For example, a useful emulsifiable concentrate formulation contains 20.0 parts by weight of the active isoxazolopyrimidine, 75 parts by weight of monochlorobenzene and 5.0 parts by weight of sulfated ethoxylated nonylphenol.

Granular formulations, wherein the toxicant is carried on or in relatively coarse particles, are usually applied without dilution to the area in which suppression of vegetation is desired. Typical carriers for granular formulations include sand, fullers earth, bentonite clays, vermiculite, perlite and other organic or inorganic materials which absorb or which may be coated with the toxicant. Granular formulations normally are prepared to contain about 5-25 percent of active ingredient and may also contain small amounts of other ingredients such as surface-active agents, including wetting agents, dispersing agents or emulsifiers; oils, including heavy aromatic naphthas, kerosene or other petroleum fractions, or vegetable oils; and/or stickers including dextrins, glue or synthetic resins.

The average particle size of the granules is usually between 150 and 2,400 microns. For example, a useful granular formulation contains 5.05 parts by weight of the active isoxazolopyrirnidin, 5.00 parts by weight of corn oil, and 89.95 parts by weight of crushed corn cobs.

Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, for example, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; ethoxylated alcohols; ethoxylated alkylphenols; sulfonated oils, ethoxylated fatty amine salts; fatty acid esters of polyhydric alcohols; and other types of surface-active agents, many of which are available in commerce, including those of the anionic, nonionic, cationic and amphoteric types. The surface-active agent, when used, normally comprises from l percent to 15 percent by weight of the herbicidal composition.

Dusts, which are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers for the toxicant, are useful formulations for soil-incorporated applications; the finely divided solids have an average particle size of less than about microns.

Pastes, which are homogeneous suspension of a finely divided solid toxicant in a liquid carrier such as water or oil, are employed for specific purposes. These formulations normally contain about 5-95 percent of active ingredient by weight, and may also contain small amounts of a wetting, dispersing or emulsifying agent to facilitate dispersion. For application, the pastes are normally diluted and applied as a spray to the area to be affected.

Other useful formulations for herbicidal applications include simple solutions of the active ingredient in a dispersant in which it is completely soluble at the desired concentration,

18 such as acetone, alkylated naphthalene, xylene or other organic solvents.

Typically herbicidal compositions in solid state (e.g. wettable powders, dusts, or granules) are packaged in paper (or plastic) bags containing, say, 2, 5, 10 or l5 pounds of the herbicidal composition and labelled with directions for the herbicidal use. Liquid herbicidal compositions (e.g. emulsiflable concentrates or pastes) are commonly packaged in quart or gallon rigid container, e.g. jars or cans, similarly labelled. The herbicidal compositions of this invention may be packaged similarly.

It is to be understood that the foregoing detailed description is merely given by way of illustration, and not by way of limitation, and that many variations may be made therein without departing from the spirit of the invention.

What I claim is:

l. A substituted isoxazolopyrimidine of the formula:

R NH

I J R wherein R and R are respectively members of the group consisting of lower (one to four carbon atoms) aliphatic hydrocarbon, lower (three to six carbon atoms)-cycloaliphatic hydrocarbon and trifluoromethyl radicals; and the herbicidally effecu've metallic and amine salts thereof.

2. A substituted lsoxazolopyrimidme of the formula:

wherein R is a member of the group consisting of methyl, ethyl, propyl and isopropyl radicals;

n is 0 or 1.

3. A substituted isoxazolopyrimidine of the formula:

' a) 3-n NE o N R wherein R is a member of the group consisting of methyl,

ethyl, propyl and isopropyl radicals;

n is 0 or 1.

4. A compound as defined in claim 1 which is 3,6- Diisopropyl-5H-isoxazolo[ 5,4-d]pyrimidin-4-one.

5. A compound as defined in claim 1 which is 6-Ethyl-3- isopropyl-5l-l-isoxazolo[5,4-d]pyrimidin-4-one.

6. A compound as defined in claim 1 which is 6-tert-Butyl- 3-isopropyl-5H-isoxazolol 5 ,4-d1pyrimidin-4-one.

7. A compound as defined in claim 1 which is 3-tert-Butyl- -6-isopropyl-5H-isoxazolo[5,4-d1pyrimidin-4-one.

. Page 1 of 9 UNITED STATES PATENT OFFICE QERTTFIQATE @F CQRREQTTQN PATENT NO. 3,679,682 DATED July 25, 1972 INVENTOR(S) Loren K. Gibbons It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 10, line 1, through Column 12,

line 61, Table I B shoul appear as follows:

Table 'I' B Preeme r 'g e n ce Pr'i'm'a ry' Evaluation of Compounds Test O'JS'lb/HCIG lgfllb/ ac-r e' 2".0 lb/a c re 4.0l'b/'a'c'r e '8','0lb'/acre Plant Species Vigor K'i l l Vi g'o r Kil l Vi'go'r' K-i'l'l Vigor Kill Vigor Kill Lima beans 5 4 0 l 80 2 80 100 Dent corn 4 O 3 0 l 0 l 0 l 60 Lettuce 4 0 3 40 l 90 l 95 100 Mustard 2 90 l 90 100 100 100 Crabgrass 3 0 3' 60 l 95 100 100 3-E'thy l 6'- 1 sop rop yl H i s'ox'a'z o1'o[5,4-'d]pyri'mid'i'n-4-one Lima beans 3 0 2 60 100 100 100 Dent corn 3 O 3 2 l l 80 Lettuce 4 0 3 50 100 100 100 Mustard 3 100 100 100 100 Crabgrass 3 50 100 100. 100 100 3Eth'y l- G-Irte't hy'l'5'H''i's'o'xa'zo'l'o'['5',4'-d]pyrimidin-4-one Lima beans 4 0 4 O 4 0 2 0 l 0 Dent corn 5 0 4 0 2 30 100 100 Lettuce 5 0 5 0 4 0 2 20 l 80 Mustard 5 0 5 0 3 30 l 80 l Crabgrass 5 0 4 0 3 0 3 20 l 95 Page of 9 UNITED STATES PATENT QFFTCE CERTTTTQATE QT QURREQTTQN Q PATENT NO. 1 3,679,682

DATED July 25, 1972 I INVENTOR(S) Loren Kn Gibbons It is certified that error appears in the ab0ve identified patent and that said Letters Patent are hereby corrected as shown below:

. 3-'Butyl- 6'e thyl5H-r'i'so'xa'zo'l'o ['5,4'-'d]pyrimidin-4-one Test 'O'Q'S l'b/a C re 'l'. 0 l b'/'a c're '2..0'l'b/a'cr'e' '4,'01Wacre 8'. Olb/acre Plant v Species Vigor 'K'i'l'l' Vigor 'K'i l l' Vi'g o'r Kill Vigor Kill Vigor Kill Lima beans 5 O 4 0 3 3 100 9 Dent corn 5 o 4 0 4 0 3 0 3 50 Lettuce 4 0 3 0 3 40 100 100 Mustard 4 O 4 0 3 100 100 Crabgrass 5 0 4 O 3 100 Q .3iit1er.t.-Bu .t y l..6 ethyl-.SH-isoxaz.o.l.o.[ 5,4--d].pyrimidin4-one Lima beans 100 100 100 100 100 Dent corn 2 20 2 20 l 40 100 100 Lettuce 100 100 100 100 100 Mustard 100 100 100 100 100 Crabgrass 100 100 r a 100 100 100 3-tert-Butyl-6-isopropyl-5H-isoxazolo[5,4d]pyrimidin- 4-one Lima beans 100 l 60 100 100 Dent corn 2 0 2 50 2 50 100 G Lettuce 100 100 100 100 Mustard 100 100 100 100 Crabgrass 3 50 100 100 100 6-te'rt-Butyl3-isopropyl-5H-isoxazolo[5,4-d1pyrimidin- Lima beans 1 75 100 100 100 Dent corn 5 O 3 0 2 3O 2 0 tree see 188 188 r88 r88 Crabgrass 1% 100 100 100 v d Page 4 01 9 UNITED STATES PATENT OFFICE QETHICATE @F CORECTION PATENT NO. 3, 7 Q DATED July 25, 1972 INVENTOR(S) Loren K. Gibbons It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below: 6-Cyclopropyl-3-propyl5H-isoxazolo 4-d] pyrimidina j r i v j r I i i I a w Test 0'..5'lb /a'c=re l 0' l=b' ac re 2 ."O l b a'c r e 4 0l b/ a'cre '8'.'0'l'b acre Plant Species Vi'g'o'r K'i'l'l Vi'g'or' K'i'll' Vigor Ki'l'l' Vigor Kill Vigor Kill [Lima beans 4 t o 2 40 100 100 100 Dent corn 4 O 3 O 3 0 3 20 2 Lettuce 100 100 100 100 100 Mustard 3 3 100 100 100 Crabgrass 4 0 3 5O 100 100 100 q 3-Isopropyl-6methyl5H-isoxazolo[5,4d]pyrimidin- 4'-one' Lima beans 4 O 3 50 100 2 100 Dent corn 4 O 3 O 3 0 2 0 l 70 Lettuce 100 100 100 100 100 qMustard 100 100 100 100 100 Crabgrass 3 l0 1 100 100 3't'e'rt-Butyl-6propyl-5H-isoxazolo[5,4-d]pyrimidin I Lima beans 4 0 2 0 100 100 2 75 Dent corn 4 0 3 0 2 0 2 30 l 70 Lettuce 4 0 3 2O 3 70 2 80 100 Mustard 3 10 100 100 100 100 Crabgrass 4 0 3 l0 3 30 100 100 Lima beans 5 gent corn 5 0 4 0 3 0 g g 0 r Msst g 8 Z 8 2 98 188 188 Qrabgrass 5 0 4 0 3 0 2 30 2 50 Page Of 9 UNITE STATES PATENT UFFICE @ETTTTQAT F EQTN PATENT NO. 3,679,682 DATED July 25, 1972 INVENTOR(S) I Loren K. Gibbons it is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Test Plant Species Lima beans Dent corn Lettuce Mustard Crabgrass Lima beans Dent corn Lettuce Mustard Crabgrass Lima beans Dent corn Lettuce Mustard Crabgrass 3-Ethyl-6-(l-methylpropyl)5H-isoxazolo[5,4-d1pyrimi- Vigor Kill. Vigor. Kill. Vi.gor...Kill Vigor Kill Vigor Kill 3 0 2 100 a l 80 3 O 2 0 2 0 2 O 4 0 3 100 100 l 90 100 l 90 100 3 0 3 8O 2 8O 2 3-Ethyl-6-(2-methylpropyl)5H-fsoxazolo[5,4d]PYrimi 3 20 3 20 2 40 2 80 100 3 0 3 0 3 0 3 0 2 0 4 0 4 0 3 0 2 20 100 l 1.00 l 90 l 4 0 4 0 I 3 O 3 30 100 6Cyclopentyl3-isopropyl-5H-isoxazolo[5,4-d1pyrimi- 5 O 5 0 5 0 4 O 3 O 5' 0 5 O 5 O 3 0 2 0 5 O 5 0 4 0 3 0 3 0 5 O 4 0 3 0 l 95 100 5 O 4 O 3 O 3 20 l 95 g Page 6 of 9 UNITED STATES PATENT OFFICE QERTIFICATE OF CQRRECTIN PATENT NO. 1 3,679,682

DATED I July 25, 1972 INVENTOR(S) Loren K. Gibbons It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Lima beans 4 3 0 3 2O 2 40 l 60 Dent corn 4 0 4 0 3 0 3 0 2 O Lettuce 4 0 3 100 100 100 Mustard 3 20 I00 100 100 100 Crabgrass 4 0 4 0 3 0 2 70 100 O '3','6 -D ime t hy l SH- i so'xa zo'lo'['5',4'-d ]'p'y'r imid i n'4-o'ne' Lima beans 5 0 5 O 5 0 5 0 4 0 Dent corn 5 0 5 O 5 O 4 0 3 40 Lettuce 5 0 5 0 5 0 4 0 3 30 Mustard 5 O 5 0 4 0 3 100 Crabgrass 5 0 5 t) 4 0 4 0 3 50 Lima beans 3 20 100 100 100 100 Dent corn 3 O 3 0 2 0 l l Lettuce l 100 100 100 100 d lustard 2 80 100 100 100 100 Crabgrass 3 0 3 50 100 100 100 3t'e'rt-Butyl-6-methyl-5H-isoxazolo[5,4-d1pyrimidinv r v r Lima beans 2 75 100 100 100 100 ent corn 3 0 3 O 2 0 2 70 100 ettuce 100 100 100 100 100 ustard l l 95 100 100 rabgrass 3 50 l 90 100 100 100 Page '7 Of 9 UNITED STATES PATENT ()FFICE QER'HFIQATE OF QREQ'H PATENT NO. 3,679,682

DATED 2 July 25, 1972 |NVENTOR(S) Loren K. Gibbons It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Test 0,5lb/acre 1.0lb/acre 2.0lb/acre 4.0lb/acre 8.0lb/acre Plant Species Vigor Kill Vigor Kill Vigor Kill Vigor Kill Vigor Kill Lima beans 4 4 O 3 100 100 Dent corn 4 0 4 O 3 0 2 0 l 60 Lettuce 3 3 30 100 100 100 Mustard 3 l0 3 100 100 100 Crabgrass 4 0 3 O 3 20 100 100 3-Propyl-6-trifluoromethyl-5H-isoxazolo[5,4-d1pyrimidin-4-one Lima beans 5 0 5 0 5 O 5 0 4 0 Dent corn 5 O 5 O 4 0 4 0 3 0 Lettuce 5 0 100 100 100 100 Mustard 5 0 5 0 4 0 3 50 100 Crabgrass 5 0 5 0 5 0 5 0 4 0 G-te'r-t-Butyl-3methy15H-isoxazolo[5,4-d]pyrimidin Lima beans 3 50 100 l 100 Dent corn 4 0 3 0 3 0 2 O 2 30 Lettuce 3 l0 2 50 100 100 100 Mustard 100 100 100 100 100 Crabgrass 3 50 2 50 100 100 100 Page 8 of 9 UNITED STATES PATENT OFFICE CERTIFICATE OF CORECTIUN PATENT NO. 1 3,679,682

DATED July 25, 1972 INVENTOR(S) Loren K. Gibbons it is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 12, line 66, should read:

Test 0.5lb/acre l.0lb/acre 2.0lb/acre 4.0lb/acre 8.0lb/acre Column 13, line 50, through Column 15, line 76 Tables I D and I E, all the chemical names should appear without a space in the middle, e..g. "3,.6Diethyl-5Hisoxazolo[5,4-d]pyrimidin-4-one".

. Page 9 of 9 UNITED STATES PATENT OFFICE @E ICATE 9F C0 QTKQN PATENT NO. 1 3,679,682

DATED July 25, 1972 INVENTOR(S) Loren K, Gibbons It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 14, line 26 in Table IE, the entry against'Dent Corn should read:

V'i'go'r' Ki l'l Vi g'o'r K i'l l Vigor 'K'i'l'l' Vi'g-o'r K'i l'l Vigor Kill Column 16, line 15 in Table IE, the chemical name should read: "6''te'r-t -Butyl3-methyl5H-isoxazolo[5,4-d]pyrimidin-4-one".

Column 16, line 23 in Table IE, the chemical name should read: "6t'ert-Butyl3propyl-5H-isoxazolo[5,4-d1pyrimidin-4-one".,

Column 16, line 44 in Table IF, the entry against Lettuce should read" e a e e Vigor K'i'l'l' V-ig'o'r K il'l V'i gor K11 1 Vigo'r Kill Vigor Kill Signed and gealed this Twentieth Day of July 1976 [SEAL] A tr es t:

RUTH C. MASON C. MARSHALL DANN Arresting Officer Commissioner ofParents and Trademarks 

2. A substituted isoxazolopyrimidine of the formula: wherein R is a member of the group consisting of methyl, ethyl, propyl and isopropyl radicals; n is 0 or
 1. 3. A substituted isoxazolopyrimidine of the formula: wherein R is a member of the group consisting of methyl, ethyl, propyl and isopropyl radicals; n is 0 or
 1. 4. A compound as defined in claim 1 which is 3,6-Diisopropyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 5. A compound as defined in claim 1 which is 6-Ethyl-3-isopropyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 6. A compound as defined in claim 1 which is 6-tert-Butyl-3-isopropyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 7. A compound as defined in claim 1 which is 3-tert-Butyl-6-isopropyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 8. A compound as defined in claim 1 which is 3-tert-Butyl-6-ethyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 9. A compound as defined in claim 1 which is 6-tert-Butyl-3-propyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 10. A compound as defined in claim 1 which is 3,6-Diethyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 11. A compound as defined in claim 1 which is 3-tert-Butyl-6-methyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 12. A compound as defined in claim 1 which is 3-Isopropyl-6-methyl-5H-isoxazolo(5,4-d)pyrimidin-4-one.
 13. A compound as defined in claim 1 which is 3-ethyl-6-tert-butyl-5H-isoxazolo(5,4-d)pyrimidin-4-one. 